Obesity continues to rise in the United States and throughout the world. Both leptin from fat cells and insulin from pancreatic B cells are created in direct proportion to body fat. Obese persons have higher levels of these two hormones than lean individuals. Recent studies show that another hormone, estrogen, also has a similar affect. When estrogen receptors in the hypothalamus of rats were destroyed, female rats ate more food, burnt less energy and became obese. Research suggests a link between estrogen and obesity, especially the dangerous accumulation of abdominal fat linked to cardiovascular disease, type-2 diabetes mellitus, and certain cancers. The abstract was submitted by Deborah J. Clegg, PhD, Assistant Professor of Psychiatry, Obesity Research Center, at the University of Cincinnati Academic Health Center, to the 234th national meeting of the American Chemical Society on August 20, 2007. Her findings will assist scientists in developing new hormone replacement therapies.

Dr. Clegg Estrogen wanted to determine the effect of reduced estrogen levels in the brain. She investigated estrogen receptor alphas (ERa) in the hypothalamus, where the brain regulates body temperature, hunger and thirst. She learned that the ventromedial nucleus (VMN) and the arcuate nucleus respond to hormones and other signals to control energy intake and expenditure. A gene-silencing technique called RNA interference allowed Dr. Clegg to shut down the alpha receptors in the VMN of female rats. The estrogen receptors in other regions of the brain were not affected. As estrogen levels decreased, so did the metabolic rate and energy levels. The rats quickly became glucose intolerant. While their caloric intake did not change, they gained considerable abdominal weight.

Dr. Clegg feels that deactivating ERa in the arcuate nucleus region of the hypothalamus may have the same effect. There are two groups of neurons in this region. One reduces food intake and the other stimulates it. Estrogen loss in this region may increase both appetite and weight.

In humans, the accumulation of abdominal fat in men and women increases their risk of cardiovascular disease, diabetes, and insulin resistance. Young women are protected from these risks while they carry their weight in their hips and saddlebags. With the onset of menopause, however, body fat is stored in the abdomen, increasing the risk of medical complications. By identifying the critical brain regions and estrogen receptors associated with weight gain and energy expenditure, scientists will one day be able to design hormone replacement therapies that will help women avoid many of the risks associated with the onset of menopause.